The studies proposed in this application will generate a new experimental mouse model for the investigation of questions concerning the clinical association of cytomegalovirus (CMV) and graft-versus-host disease (GVHD). Mice will be infected with murine cytomegalovirus (MCMV) and monitored until infectious virus is no longer detectable (chronically infected). These animals will subsequently receive an allogeneic bone marrow transplant. The major objective of the study is to investigate how donor T-cells effect the outcome of an allogeneic bone marrow transplant in recipients previously infected target tissues including the lung. Virus expression will be assessed by cellular (plaque) and molecular (PCR) assay and examined with respect to donor effector function. Clinical signs and histopathology of GVHD and MCMV target issues will be assessed to correlate the presence and levels of virus with the pathogenesis occurring following allogeneic BMT. In tissues where viral expression precedes or coincides with cellular infiltrates, CD3+ T-cells will be isolated and characterized by phenotype to identify the infiltrating populations and compare to populations identified in non-infected recipients. The infiltrates will be assessed functionally for anti-host and anti-viral reactivity. To address how donor cells can affect virus expression following transplant, functionally defective T-cells for the production of interferon-gamma and mediation of cytotoxicity via perforin and/or FasL will be transplanted. Finally, bone marrow transplants utilizing donor T-cells specific for non-self ('host') MHC plus MCMV will be performed to test the hypothesis that such cells can control MCMV infection and diminish GVHD post-transplant.